section 8.1
Diagnosis and Prognosis of Disease
123
TABLE 8-2
Properties o f Cardiac Markers Used in the Evaluation o f Acute Myocardial Infarction (AMI)
Marker
Molecular
Weight
(Daltons)
Elevation
after
AMI
(Hours)
Peak
Elevation
(Hours)
Return to
Normal Levels
(Hours or Days)
Clinical Usefulness
Myoglobin
17,200
1-3
4-6
20-24 hrs
Earliest marker; not cardiac specific.
Total CK
8 6 , 0 0 0
4-8
12-24
36-48 hrs
A relatively early marker; not cardiac specific.
CKMB
8 6 , 0 0 0
4-6
12-24
24^18 hrs
A relatively early marker; has higher cardiac
specificity over total CK.
Cardiac
Troponin T
39,700
4-6
18-36
5-14 days
A relatively early marker; cardiac specific; how-
ever elevated in diseases of regeneration
of skeletal muscle and chronic renal disease.
Cardiac
Troponin I
24,000
4-6
12-24
5-9 days
A relatively early marker; cardiac specific.
LDH
135,000
8 - 1 2
48-72
10-15 days
Late marker; not cardiac specific; LD1/LD2
determination increases cardiac specificity.
intracellular enzymes. These changes can result from a
decrease in intracellular ATP concentration due to any of
the following conditions: deficiency of one or more of the
enzymes needed in ATP synthesis (e.g., pyruvate kinase in
red blood cells); glucose deprivation; localized hypoxia;
and high extracellular K+ (ATP depletion results from in-
creased activity of the Na+, K+-ATPase in the cell plasma
membrane required to maintain the proper K+/Na+ ratio
between the intracellular and extracellular environments).
Localized hypoxia can result from poor blood flow, the
result of obstruction of blood vessels responsible for the
territorial distribution of the blood (a condition known as
ischemia).
Ischemia may result from narrowing of the lu-
men of the blood vessels (e.g., deposition of lipids in the
vessel wall, which leads to atherosclerosis; see Chapter 20)
or from formation of blood clots within the vessels. Is-
chemic necrosis leads to formation of an infarct (the pro-
cess is called
infarction).
When cells of the myocardium
die as a result of severe ischemia, the lesion is known as a
myocardial infarct.
The amount of enzymes released depends on the degree
of cellular damage, the intracellular concentrations of the
enzymes, and the mass of affected tissue. The nature of
the insult (viral infection, hypoxia, or surgical, chemical,
or mechanical trauma) has no bearing on the enzymes
released into the circulation.
The nature of the enzymes released also reflects the
severity of the damage. Mild inflammatory conditions are
likely to release cytoplasmic enzymes, whereas necrotic
conditions yield mitochondrial enzymes as well. Thus,
in severe liver damage (e.g., hepatitis), the serum as-
partate aminotransferase (AST) level is extremely high
(much greater than that of alanine aminotransferase)
because the mitochondrial isoenzyme of AST is re-
leased in addition to the corresponding cytoplasmic
isoenzyme.
The amount of enzyme released into the plasma from
an injured tissue is usually much greater than can be
accounted for on the basis of tissue enzyme concentra-
tion and magnitude of injury. Loss of enzymes from cells
may stimulate further synthesis of enzymes. In experi-
mental animals, biliary occlusion leads to increased syn-
thesis of hepatic alkaline phosphatase. Many drugs cause
an increase in drug-metabolizing enzymes as a result of
an increase in
de novo
synthesis (i.e., enzyme induc-
tion). These drug-metabolizing enzymes, located in the
smooth endoplasmic reticulum (microsomal fraction; see
Chapter 2) of liver and other tissues, catalyze the fol-
lowing chemical reactions: hydroxylation, demethylation,
deethylation, acetylation, epoxidation, deamination, glu-
curonidation, and dehalogenation. Thus, serum levels of
some of these enzymes may be elevated following expo-
sure to enzyme-inducing agents, such as ethanol, barbi-
turates, phenytoin, and polycyclic hydrocarbons. While
plasma levels of enzymes can become elevated because
of tissue injury, the levels may drop (in spite of continued
progress of the injury) to normal (or below normal) lev-
els when the blood circulation is compromised or when
the functional part of the tissue is replaced by repair
or nonfunctional tissue (e.g., connective tissue, as in
extensive fibrosis of the liver in the disease known as
cirrhosis).
